Modified polynucleotides for the production of nuclear proteins

Patent metadata

Field	Value
Publication number	US-9283287-B2
Application number	US-201514694357-A
Country	US
Kind code	B2
Filing date	Apr 23, 2015
Priority date	Apr 2, 2012
Publication date	Mar 15, 2016
Grant date	Mar 15, 2016

Abstract

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

First claim

We claim:

1. An mRNA encoding SEQ ID NO: 3906, wherein said mRNA comprises a coding region having at least 80% identity to SEQ ID NO: 15012.

2. The mRNA of claim 1 , wherein the mRNA comprises at least one untranslated region 5′ relative to the coding region and at least one untranslated region 3′ relative to the coding region.

3. The mRNA of claim 2 , wherein the 5′ untranslated region is heterologous to the coding region of the mRNA.

4. The mRNA of claim 2 , wherein the 3′ untranslated region is heterologous to the coding region of the mRNA.

5. The mRNA of claim 2 , wherein the 5′ untranslated region and the 3′ untranslated region are heterologous to the coding region of the mRNA.

6. The mRNA of claim 2 , wherein the mRNA comprises at least two stop codons.

7. The mRNA of claim 1 , wherein the coding region has at least 90% identity to SEQ ID NO: 15012.

8. The mRNA of claim 7 , wherein the coding region is selected from the group consisting of SEQ ID NO: 15012, 15008, 15011, 7604, 7607 and 7608.

9. The mRNA of claim 1 , wherein the coding region has at least 95% identity to SEQ ID NO: 15012.

10. The mRNA of claim 9 , wherein the coding region is selected from the group consisting of SEQ ID NO: 15012, 15008 and 15011.

11. The mRNA of claim 1 , wherein the coding region consists of SEQ ID NO: 15012.

12. A pharmaceutical composition comprising the mRNA of claim 1 and a pharmaceutically acceptable excipient.

13. The pharmaceutical composition of claim 12 , wherein the pharmaceutically acceptable excipient is selected from a solvent, aqueous solvent, non-aqueous solvent, dispersion media, diluent, dispersion, suspension aid, surface active agent, isotonic agent, thickening or emulsifying agent, preservative, lipid, lipidoids liposome, lipid nanoparticle, core-shell nanoparticles, polymer, lipoplex, peptide, protein, cell, hyaluronidase, and mixtures thereof.

14. The pharmaceutical composition of claim 13 , where the pharmaceutical composition comprises a lipid and wherein said lipid is selected from DLin-DMA, DLin-K-DMA, DLin-KC2-DMA, 98N12-5, C12-200, DLin-MC3-DMA, DODMA, DSDMA, DLenDMA, reLNPs, PLGA, PEGylated lipids and mixtures thereof.

15. A method of producing a polypeptide of interest in a mammalian cell, tissue or organism comprising contacting said cell, tissue or organism with the mRNA of claim 1 .

16. The method of claim 15 , wherein the mRNA is formulated.

17. The method of claim 16 , wherein the formulation comprises a lipid which is selected from the group consisting of DLin-DMA, DLin-K-DMA, DLin-KC2-DMA, 98N12-5, C12-200, DLin-MC3-DMA, DODMA, DSDMA, DLenDMA, reLNPs, PLGA, PEGylated lipids and mixtures or combinations thereof.

18. The method of claim 15 , wherein the contacting is a route of administration selected from the group consisting of intramuscular, intradermal, intravenous and subcutaneous.

19. The method of claim 18 , wherein the route of administration is intramuscular.

20. The method of claim 15 , wherein the mRNA comprises at least one untranslated region 5′ relative to the coding region and at least one untranslated region 3′ relative to the coding region.

21. The method of claim 20 , wherein the 5′ untranslated region is heterologous to the coding region of the mRNA.

22. The method of claim 20 , wherein the 3′ untranslated region is heterologous to the coding region of the mRNA.

23. The method of claim 20 , wherein the 5′ untranslated region and the 3′ untranslated region are heterologous to the coding region of the mRNA.

24. The method of claim 20 , wherein the mRNA comprises at least two stop codons.

Assignees

• Moderna Therapeutics Inc

Inventors

• Chakraborty Tirtha
• De Fougerolles Antonin
• Weiss Ron

Classifications

• A61K31/7088

  Compounds having three or more nucleosides or nucleotides · CPC title

• A61K38/193

  Colony stimulating factors [CSF] · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K48/0066 Primary

  Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid · CPC title

• A61K38/215

  IFN-beta · CPC title